Maternal dietary n-3 PUFA deficiency leads to sex-specific alterations in placental and cerebral fatty acid profiles and in oxylipin profiles in the developing mouse brain

Marchaland F(1), Martinat M(1), Di Miceli M(2), Grégoire S(3), Rossitto M(1),
Morel L(1), Aubert A(1), Séré A(1), Delpech JC(1), Joffre C(1), Acar N(3),
Bazinet RP(4), Layé S(5).

Author information:
(1)Institut Nutrition et Neurobiologie Intégré (NutriNeurO), INRAE, Université
de Bordeaux, UMR 1286, Bordeaux, France.
(2)Institut Nutrition et Neurobiologie Intégré (NutriNeurO), INRAE, Université
de Bordeaux, UMR 1286, Bordeaux, France; School of Biomedical Sciences, Faculty
of Biological Sciences, University of Leeds, Leeds, LS2 9JT, United Kingdom.
(3)Eye & Nutrition Research Group, Centre des Sciences du Goût et de
l’Alimentation, CNRS, INRAE, Institut Agro, Université Bourgogne Europe,
F-21000, Dijon, France.
(4)Department of Nutritional Sciences, Faculty of Medicine, University of
Toronto, Toronto, ON, M5S 1A1, Canada.
(5)Institut Nutrition et Neurobiologie Intégré (NutriNeurO), INRAE, Université
de Bordeaux, UMR 1286, Bordeaux, France. Electronic address:
.

Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly arachidonic acid
(AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), are essential for optimal
neurodevelopment through their effect on neuronal proliferation, neurite
outgrowth and synaptogenesis. Emerging evidence highlights that brain PUFAs are
metabolized in oxylipins, the bioactive oxidized PUFA metabolites known to
regulate inflammatory processes. Recent data highlighted that both PUFA and
oxylipin profiles are modulated in the brains of adult male mice by dietary PUFA
content. However, little is known on the impact of maternal dietary n-3 PUFA
intake during the perinatal period and the neurodevelopmental profile of brain
fatty acids and associated oxylipins in mouse offspring, and whether these
effects differ between sexes. To address this question, we first measured fatty
acid levels in the placenta and embryonic brain of male and female mice at
embryonic day (E)17.5 of mothers fed an n-3 PUFA-sufficient diet (based on
canola oil, rich in the n-3 precursor alpha-linolenic acid) or an n-3
PUFA-deficient diet (based on sunflower oil, rich in the n-6 precursor linoleic
acid) in n-3 PUFAs starting at E0. Then, fatty acids and oxylipins were measured
at different post-natal stages, in the brain at postnatal day (P)0 and P7, and
in the hippocampus at P14 and P21, in both male and female mouse offspring. Our
results show that maternal n-3 PUFA dietary deficiency alters fatty acid
profiles as early as E17.5 in both the placenta and the brain. Furthermore,
dietary intervention affects both fatty acid and oxylipin profiles throughout
postnatal brain development, with notable sex-specific differences. These
findings highlight the importance of maternal n-3 PUFA intake during the
perinatal period for establishing and maintaining PUFA and oxylipin profiles in
the developing brain.

Copyright © 2026. Published by Elsevier B.V.

DOI: 10.1016/j.biochi.2026.07.010
PMID: 42480752

Conflict of interest statement: Declaration of competing interest We have no
conflict of interest to declare.

Auteurs Bordeaux Neurocampus